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Related Experiment Videos

TRAIL regulates normal erythroid maturation through an ERK-dependent pathway.

Paola Secchiero1, Elisabetta Melloni, Markku Heikinheimo

  • 1Dept of Morphology and Embryology, Human Anatomy Section, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, Italy. secchier@mail.umbi.umd.edu

Blood
|September 13, 2003
PubMed
Summary

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) impacts human erythropoiesis by inducing apoptosis and inhibiting erythroblast maturation via the ERK1/2 pathway. Inhibiting ERK1/2 rescues erythroid differentiation.

Area of Science:

  • Hematology
  • Cell Biology
  • Immunology

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a key mediator of apoptosis.
  • Erythropoiesis, the process of red blood cell formation, is crucial for oxygen transport.
  • Understanding TRAIL's role in erythropoiesis can reveal new therapeutic targets.

Purpose of the Study:

  • To investigate the biologic activity of TRAIL on human erythropoiesis.
  • To identify TRAIL receptors and intracellular pathways involved in its effects on erythroid cells.
  • To determine the impact of TRAIL on erythroid differentiation and maturation.

Main Methods:

  • Generation of glycophorin A (GPA)+ erythroid cells from human cord blood (CB) CD34+ progenitor cells in serum-free culture.

Related Experiment Videos

  • Analysis of TRAIL receptor expression (TRAIL-R1, -R2, -R3, -R4) during erythroid differentiation.
  • Treatment with recombinant TRAIL and pathway inhibitors (z-VAD-fmk, PD98059, SB203580) to assess effects on apoptosis and differentiation.
  • Main Results:

    • TRAIL-R1 and TRAIL-R2 were expressed on erythroid cells, while TRAIL-R3 and -R4 were not detected.
    • Recombinant TRAIL induced apoptosis and inhibited the maturation of erythroblasts.
    • TRAIL significantly stimulated the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, which mediated its negative effects on erythroid maturation.

    Conclusions:

    • TRAIL exerts biologic activity on human erythropoiesis, primarily through TRAIL-R2.
    • The ERK1/2 pathway is a critical mediator of TRAIL's inhibitory effects on erythroid differentiation.
    • Targeting the ERK1/2 pathway may offer a strategy to modulate TRAIL-induced inhibition of erythropoiesis.